The objective of the proposed research is the development of the B lymphocyte lineage. A major resource in our research will be the I.29 B cell lymphoma because of several unusual attributes: 1) the tumor expresses two immunoglobulin isotypes, IgM and IgA; 2) preliminary evidence suggests differentiation in the direction micron plus yields micron plus alpha plus yields alpha plus; 3) a cloned cell line derived from I.29 responds to LPS by secreting IgA; 4) the immunoglobulin gene structure shows evidence for rearrangement of CH from its germline configuration and deletion in the terminally differentiated I.29 cell type committed to IgA only. Thus the study of the I.29 tumor from the immunogenetics, cell biological, and molecular points of view affords unique opportunities to learn about the differentiation of B cells from the immunocompetent state to the antibody secreting cells. Certain feature i.e., lack of "mainstream" markers CR and delta, expression of two isotypes, and the potential for progression to immunoglobulin secreting cells suggest a likeness with memory B cells worthwhile for exploration. Serological definition of an IgA allotype and the structural differences seen in membrane-associated versus secreted IgA will be two other profitable areas of research. But perhaps the most exciting aspects are the regulatory mechanisms of CH switching. Our second resource is a large collection of monoclonal antibodies. Some of these define new B cell surface antigens, with which we hope to gain entry into differentiation of early B progenitor cells and to clarify the question of whether or not the B cell lineage possesses a certain measure of autonomy (i.e., is dependent on lineage-specific stem cells). Methods of study will involve bone marrow cell separation and/or immune elimination procedures based on surface antigens of pre-B cells. Development of B lymphocytes will then be followed in congenic mouse strains reconstituted with treated marrow cells.